Doctors from London University have revealed details of what they believe is the largest amount of ecstasy ever consumed by a single person. Consultants from the addiction centre at St George's Medical School, London, have published a case report of a British man estimated to have taken around 40,000 pills of MDMA, the active ingredient in ecstasy, over nine years. The heaviest previous lifetime intake on record is 2,000 pills.

Though the man, who is now 37, stopped taking the drug seven years ago, he still suffers from severe physical and mental health side-effects, including extreme memory problems, paranoia, hallucinations and depression. He also suffers from painful muscle rigidity around his neck and jaw which often prevents him from opening his mouth. The doctors believe many of these symptoms may be permanent.

The man, known as Mr A in the report in the scientific journal Psychosomatics, started using ecstasy at 21. For the first two years his use was an average of five pills per weekend. Gradually this escalated until he was taking around three and a half pills a day. At the peak, the man was taking an estimated 25 pills every day for four years. After several severe collapses at parties, Mr A decided to stop taking ecstasy. For several months, he still felt he was under the influence of the drug, despite being bedridden.

Hallucinations

His condition deteriorated and he began to experience recurrent tunnel vision and other problems including hallucinations, paranoia and muscle rigidity. "He came to us after deciding that he couldn't go on any more," said Dr Christos Kouimtsidis, the consultant psychiatrist at St George's Medical School in Tooting who treated him for five months. "He was having trouble functioning in everyday life."

The doctors discovered that the man was suffering from severe short-term memory problems of a type usually only seen in lifetime alcoholics. But evaluating the full extent of his condition was difficult as his concentration and attention was so impaired he was unable to follow the simple tasks involved in the test.

"This was an exceptional case. His long- term memory was fine but he could not remember day to day things - the time, the day, what was in his supermarket trolley," said Dr Kouimtsidis. "More worryingly, he did not seem aware himself that he had these memory problems."

With no mental illness in his family and no prior psychiatric history, the doctors concluded that his unique condition was direct result of his intense ecstasy use.

"This is obviously an extreme case so we should not blow any observations out of proportion," says Dr Kouimtsidis. "But if this is what is happening to very heavy users, it might be an indication that daily use of ecstasy over a long period of time can lead to irreversible memory problems and other cognitive deficits."

For 10 years, MDMA has been suspected of causing these kinds of effects in heavy users. It is thought to be due to its disruption of the regulation of serotonin, a brain chemical believed to play a role in mood and memory. It remains unclear whether these effects are the result of permanent neurotoxic damage or just temporary reversible alterations in the brain.

A special two-part MDMA study in recent issues of the Journal of Psychopharmacology (available online at sagepub), suggests long-term side-effects may be temporary. The researchers from the University Of Louisiana could find no significant relationship between depression and recreational ecstasy use.

In the case of Mr A, a structural MRI brain scan failed to show any obvious damage or atrophy in his brain. However, these results, says Dr Kouimtsidis, are difficult to interpret. "A scan of this type is not sensitive enough," he said.

Such limitations in brain scanning technology, along with ethical and legal barriers to giving MDMA to human test subjects, have limited direct observation of the drug's effects in humans.

Instead, scientists have had to use recreational drug users as subjects in their studies. Conclusions from this are often flawed because few, if any, drugs users use ecstasy in isolation.

Cannabis user

Mr A was also a heavy cannabis user, and when he was encouraged to decrease his use, his paranoia and hallucinations disappeared and his anxiety abated. But his memory and concentration problems remained, leading the doctors to suspect that these may be permanent disabilities.

When he was admitted to a specialist brain injury unit and put on anti-psychotic medication, he did start to show some improvement. "Unfortunately, he discharged himself before we were able to complete the assessment," says Dr Kouimtsidis. "We continued to support him. But he started to use cannabis again and he dropped out. We tried to re-engage him but we lost him about a year ago."

The Guardian made several attempts to find the man without success.

Effects of ecstasy

MDMA is one of the most intensely studied recreational drugs in history. But despite thousands of research papers and studies, scientific evidence on the side-effects remains inconclusive.

Death by overdose

Undoubtedly, large amounts of ecstasy can lead to over-heating which in turn, in rare cases, can trigger fatal heat stroke. Many factors contribute: number and strength of pills taken, environment, alcohol-consumption, body weight - but women seem more at risk. The bulk of ecstasy-related deaths around the world have been young women.

Water-poisoning

Panicking users, fearing they are overdosing, drink too much water and provoke hyponaetraemia (water-poisoning). Leah Betts died after drinking 14 pints in just 90 minutes. The recommended amount of water to drink per hour is one pint.

Toxic reactions

Much of the reports of toxic reactions are muddled with overdose or water-poisoning deaths. There is no clear evidence that some people suffer allergic reactions to ecstasy. However, around 10% of Western users do lack a key liver enzyme CYP2D6 needed to break down MDMA. This may make them more sensitive to the effects and more prone to accidental overdose.

Depression

Many weekend users report a mid-week mood dip. This is suspected to be related MDMA's effect on serotonin, but hard evidence is lacking. In heavy users, dips can turn to crashes and depression. However studies suggest this effect reverses after a 2-3 month abstinence.

Positive effects

Users still claim "long lasting improvements in self-awareness, self-esteem, openness and insight into personal problems", reports the study from the University Of Louisiana. In the US, research continues into the use of MDMA-assisted psychotherapy to treat Post Traumatic Stress Disorder.